Journal of Medical Mycology xxx (xxxx) xxx
Contents lists available at ScienceDirect
Journal of Medical Mycology
jo urnal homepage: www.elsevier.com
General review
Estimates of serious fungal infection burden in Coˆte d’Ivoire and country health profile
a, a a a a a b
D. Koffi *, I.V. Bonouman , A.O. Toure , F. Kouadjo , M.R.E. N’Gou , K. Sylla , M. Dosso , c,1
D.W. Denning
a
Parasitology and mycology department, Institut Pasteur de Coˆte d’Ivoire, 01 PoBox 490 Abidjan 01, Coˆte d’Ivoire
b
Bacteriology and virology department, Institut Pasteur de Coˆte d’Ivoire, Abidjan, Coˆte d’Ivoire
c
Manchester Fungal Infection Group, faculty of medicine, biology and health, university of Manchester and Manchester academic health science centre,
Manchester, UK
A R T I C L E I N F O A B S T R A C T
Article history: Due to limited access to more powerful diagnostic tools, there are few data on the burden of fungal
Received 15 September 2020
infections in Coˆte d’Ivoire, despite a high HIV and TB burden and many cutaneous diseases. Here we
Received in revised form 12 November 2020
estimate the burden of serious fungal infections in this sub-Saharan country with a health profiling
Accepted 17 November 2020
description. National demographics were used and PubMed searches to retrieve all published articles on
Available online 21 November 2020
fungal infections in Coˆte d’Ivoire and other bordering countries in West Africa. When no data existed, risk
populations were used to estimate frequencies of fungal infections, using previously described
Keywords:
methodology by LIFE (www.LIFE-Worldwide.org). The population of Coˆte d’Ivoire is around 25 million;
Fungal disease
37% are children (14 years), and 9% are > 65 years. Tinea capitis in children is common, measured at
Coˆte d’Ivoire
Cryptococcosis 13.9% in 2013. Considering the prevalence of HIV infection (2.6% of the population, a total of 500,000)
Burden disease and a hospital incidence of 12.7% of cryptococcosis, it is estimated that 4590 patients per year develop
Histoplasmosis cryptococcosis. For pneumocystosis, it is suggested that 2640 new cases occur each year with the
Candidiasis prevalence of 11% of newly diagnosed HIV adults, and 33% of children with HIV/AIDS. Disseminated
AIDS
histoplasmosis is estimated a 1.4% of advanced HIV disease – 513 cases. An estimated 6568 news cases of
TB
chronic pulmonary aspergillosis (CPA) occur after pulmonary tuberculosis (a 5-year prevalence of
6568 cases [26/100,000]). Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with
fungal sensitisation (SAFS) were estimated in 104/100,000 and 151/100,000 respectively, in 1,152,178
adult asthmatics. Vulvovaginal candidiasis (VVC) is common and recurrent VVC affects 6% of women in
their fertile years – 421,936 women. An unknown number develop candidaemia and invasive
aspergillosis. The annual incidence of fungal keratitis is estimated at 3350. No cases of sporotrichosis,
mucormycosis and chromoblastomycosis are described, although some cases of mycetoma and
Conidiobolus infection have been reported. This study indicates that around to 7.25% (1.8 million) of the
population is affected by a serious fungal infection, predominently tinea capitis in children and rVVC in
women. These data should be used to inform epidemiological studies, diagnostic needs and therapeutic
strategies in Coˆte d’Ivoire.
C
2020 Elsevier Masson SAS. All rights reserved.
Introduction to species that belong to one of these four genera: Cryptococcus,
Candida, Aspergillus or Pneumocystis. Epidemiological data for
Invasive fungal disease has a high attributable mortality unless fungal infections are poor because many are misdiagnosed and
diagnosed and treated promptly and appropriately. Nearly statistics are extrapolated from few (mostly geographically
2 million people die from invasive fungal infections each year in localized) studies.
the world [1]. Over 90% of fungal infection-related deaths are due Coˆte d’Ivoire (or Ivory Coast) is located in West Africa south of
the Sahara between 10 degree North latitude, 4 and 8 degree West
2
longitude. It has an area of 322,462 km and is bounded to the west
* Corresponding author.
by Liberia and Guinea-Conakry, to the north by Mali and Burkina
E-mail address: davidkoffi[email protected] (D. Koffi).
1
In association with the LIFE program at www.LIFE-Worldwide.org. Faso, to the east by Ghana and to the south by the Gulf of Guinea. https://doi.org/10.1016/j.mycmed.2020.101086
C
1156-5233/ 2020 Elsevier Masson SAS. All rights reserved.
D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx
The population of Coˆte d’Ivoire is characterized by a growth rate papers. Cryptococcal meningitis (CM) was estimated in adults only
of 2.6% per year and by the high proportion of its youth (41.5%) (it rarely occurs in children) at a rate of 12.7% among adult HIV/
[2]. The health status of the population is marked by high maternal AIDS patients with CD4 less than 200/mL [19]. PCP frequency was
and infant-juvenile mortality, partly due to inadequate health estimated by assuming 11% of newly diagnosed HIV/AIDS adults
services. The epidemiological profile is dominated by a high (risk spread over 2 years) and 33% HIV/AIDS children at risk (25% of
prevalence of HIV among those over 15 years of age as well as a those not on antiretroviral therapy) [20,21]. Disseminated histo-
high incidence of malaria among children under 5 and tuberculosis plasmosis was estimated from an autopsy study published in 1994
in the population, respectively 2.6% [3], 189.9 per 1000 (Annual [22], and assumed to relate to all advanced HIV cases in the country
Report on the Health Situation 2018) and 85 per 100,000 (80,000) over a 2 year risk period.
inhabitants (Annual TB notification case 2018) [4]. The national Regarding invasive fungal infections associated with hospital
health priorities are these three diseases (HIV, TB and malaria) and care (notably candidiasis and aspergillosis), we considered
recently the novel coronavirus disease 2019 (COVID-19) absorbing hematology malignancies [23], lung cancer [18], chronic obstruc-
all the funds allocated to the health system and hiding the urgency tive pulmonary disease (COPD) [24], ICU and assumed peritonitis
of opportunistic infections such as severe fungal diseases (SFIs). surgical patients based on neighbouring country data [25]. No
One of the best documented examples of underfunding for transplantation procedures are currently done in Coˆte d’Ivoire. For
fungal diseases is cryptococcosis. This disease is currently chronic infections, mainly chronic pulmonary aspergillosis (CPA),
responsible for 15–20% of deaths in individuals with AIDS, and we used the annual incidence of TB to calculate a annual incidence,
yet in 2015 it received 1% of the funding allocated to tuberculosis as described previously [14–16]. This was then used to compute a
[5]. Remedying this situation requires more advocacies by the five-year prevalence assuming a 15% annual mortality or surgical
infectious disease community as well as more studies document- cure rate. We also assumed that 67% of all CPA cases had prior TB as
ing the local, national and global burden of fungal diseases and the underlying disease. Invasive aspergillosis (IA), CPA and allergic
their impact on human health. bronchopulmonary aspergillosis (ABPA) and severe asthma with
Several studies documenting fungal disease in Coˆte d’Ivoire are fungal sensitization (SAFS) were estimated in adults only. Adult
published. Oral Candida infections were reported in paediatrics and asthma data came from To et al. as part of the World Health Survey
adult patients [6]. Reports on Aspergillus [7,8] and Pneumocystis on asthma [17]. We assumed that 2.5% of adult asthmatics had
pneumonia (PCP) infections are limited to few cases [9,10]. Asthma ABPA [26] and 30% of the worst 10% of asthmatics had SAFS,
is the most common chronic respiratory disease with hospitalisa- supported by a recent review on asthma in Africa [27].
tion rate of 5% [11] and allergic rhinitis (which may be partly fungal Tinea capitis prevalence was estimated based on a local study in
in aetiology) was the most common allergic disease [12]. school children [28]. Fungal keratitis annual incidence was
Estimates of the impact of diseases on public health, generally extrapolated from East Africa [29].
referred to as burden of disease, are valuable inputs for public
health authorities, developing appropriate surveillance of fungal
diseases and setting policy priorities. Many estimates of the Results and discussion
burden of serious fungal diseases are now published for over
60 countries with populations > 1 million [13]. Disease burden Population profile
should be considered as the underlying basis for health care
prioritisation in Coˆte d’Ivoire. The total population of Coˆte d’Ivoire was 22,671,331 inhabi-
Here we report on the burden of fungal disease in Coˆte d’Ivoire tants according to the results of the General Population and
focusing in particular on prevalence data and the reliability of Housing Census (RGPH) of 2014. In 2018, it is estimated at
current estimates. These data will contribute to the global SFIs 25,195,140 inhabitants (the basis of our estimates). About 48.4%
estimation project and awareness campaign, help reframe health are females and 48% of population live below the poverty line.
policy by bringing a numerical estimate for expanded advocacy, Poverty is unequally distributed among the regions of Coˆte d’Ivoire.
increased research, and improved laboratory diagnostic capacity The level of poverty varies from 22.7% in urban areas to 71.7% in
for the fighting of fungal infection. rural areas [30]. Moreover, with the scarcity of public resources,
investments in basic social services (health, education, infrastruc-
ture, etc.) have fallen considerably, leading to a decrease in the
Methods supply of these services. In terms of health resources, Coˆte d’Ivoire
had 2023 primary health care institutions (PHCI), 82 general
The methodology adopted is that previously described [14– hospitals and 17 regional hospitals, i.e. one PHCI for 12,006
16]. Initially, we performed a PubMed search using the Medical inhabitants and one reference hospital for 173,490 inhabitants
Subject Headings terms. Keywords were combined using the [31].
Boolean operator AND and OR. Search details are: (‘‘mycoses’’
[MeSH Terms] or ‘‘mycoses’’ [all fields] or (‘‘fungal’’ [all fields] and Overall disease profile
‘‘infection’’ [all fields]) or ‘‘fungal infection’’ [all fields]) and (‘‘Coˆte
d’Ivoire’’ [MeSH terms] or (‘‘cote’’ [all fields] and ‘‘d’Ivoire’’ [All In 2016, the incidence of endemic diseases (malaria, acute
Fields]) or ‘‘Coˆte d’Ivoire’’ [all fields] or (‘‘ivory’’ [all fields] and respiratory diseases, HIV/AIDS, tuberculosis) has declined, with the
‘‘coast’’ [all fields]) or ‘‘ivory coast’’ [all fields]). exception of diarrhea and sexually transmitted infections, which
Demographic data were obtained from the ‘‘Institut National de are on the rise. The WHO estimated the number of malaria cases at
la Statistique-Coˆte d’Ivoire’’ based on the 2014 Housing and 7,890,000 (5,720,000–10,740,000) in 2016. Since 1995, a National
Population Census [2]. For many estimations, we used specific Tuberculosis Program has been established to organize the fight
populations at risk (HIV/AIDS patients [3], patients with pulmo- against TB on a national scale. The tuberculosis notification rate in
nary TB [PTB] [4], asthma [17], cancer [18], burn patients [4], and 2016 was 89 notifications per 100,000 inhabitants, compared to
patients receiving critical care) to derive national incidence or 98 per 100,000 inhabitants in 2015. Of 21,299 tuberculosis cases,
prevalence estimates of SFIs, using validated data from the country 4608 (21.6%) were found to be HIV-positive [31].
or others nearby, if available. The incidence of chronic superficial The total prevalence of HIV infection in 2018 was 2.6% [3]. At
mycoses as obtained from those reported in the PubMed-retrieved the level of care for HIV patients, 44% (1013 sites) of health
2
D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx
Table 1
public sector is 2.7 midwives per 3000 women of reproductive age
HealthTechnical plateform and equipment available in the country (RASS 2018).
(WRA). The WHO minimum standards for human resources in
Technical plateform and equipment 2017 2018 health (1 doctor per 10,000 inhabitants, 1 nurse per 5,000
inhabitants and 1 midwife for 3,000 WRA) were reached in
Public lab of medical biology 231 253
Operating theater 89 99 2018 [31].
Ambulance 536 629 Otherwise, the budget granted by the State of Coˆte d’Ivoire to
Blood transfusion centers 162 162
the Ministry of Health and Public Hygiene fell from USD
Radiology department 84 85
$665,138,840 in 2017 to $650,292,813 in 2018, a decrease of
$14.8 million (À2.22%). This budget represents 5.3% of the general
State budget in 2018. This is lower than the commitments made by
the State of Coˆte d’Ivoire at the Abuja (Nigeria) summit in
2001 which is to devote 15% of the general state health budget [31].
facilities offered antiretroviral (ARV) care and treatment services.
There were 252,125 patients on ARVs including 12,347 children Mycology diagnostics
(4.9%) and 239,778 adults.
With regard to cancer in Coˆte d’Ivoire, 15,000 new cases are Only few laboratories (5) are capable of doing diagnostic tests
expected each year. Among these cancers, it is estimated that for fungal infection with conventional methods (culture, direct
271 cases of lung cancer (5-year prevalence) are diagnosed each examination), antifungal susceptibility testing and/or innovative
year, or 1.09% of all cancers [18,32]. technical detection or for identification (PCR, MALDI-TOF). India
ink microscopy in cerebrospinal fluid is the principal means of
Healthcare facility profile and human resources making the diagnosis of cryptococcal meningitis. Recent years
have seen the introduction of cryptococcal, Histoplasma and
Coˆte d’Ivoire registered 6732 functioning hospital beds in Aspergillus antigen lateral flow assays, as well as Elisa based
2018. The estimated number of critical care beds in 2018 was 673 assays. Only the first is available in Coˆte d’Ivoire and is not
(assuming 10% of hospital beds are occupied by critically ill extensively used. An Aspergillus antibody point of care assay with
patients). Transplants programs (solid organ and hematopoietic excellent sensitivity and specificity [33] has also been launched in
stem cell) do not exist in Coˆte d’Ivoire and there is no nationwide the last 2 years and is not yet available. All of these tests are WHO
registry of surgeries undertaken. essential diagnostics.
In terms of the technical platform and existing health A solution of choice for the early diagnosis of PCP in health
equipment (shown in Table 1), there were a total number of facilities without fiberoptic bronchoscopy is the examination of
99 operating theaters, 253 public medical biology laboratories, expectorated sputum or induced by inhalation of a hypertonic
85 radiology units, 629 ambulances and 162 blood transfusion solute [34]. Detection of Pneumocystis jirovecii in sputum or
centers in public health establishments in 2018 compared to bronchoalveolar lavage fluid can be by direct microscopy using
2017. However, it should be noted that at the level of health Gomori Methenamine Silver (GMS) or calcofluor white stain,
districts: 8.1% register at least one non-functional medical device immunoflurescence or PCR. Pneumocystis PCR is the most sensitive
in their public biology laboratory, 18.6% do not have an operating technique, is now a WHO essential diagnostic and is the only
theater, 26.7% do not have any radiology service and 2.3% do not means of diagnosing pneumocystosis in children [35]. None these
have a blood transfusion center [4]. Only few (9) centres undertake techniques are currently used in Coˆte d’Ivoire.
bronchoscopy with 40% belong to the private sectors and almost all
are based in Abidjan. Incidence and prevalence of serious fungal infections
Also in 2018, the Ministry of Health and Hygiene recorded a
ratio of physicians providing healthcare in the public sector of About 7.25% (1,827,204) Ivorians were estimated to be affected
1.4 physicians per 10,000 inhabitants. The ratio of nurses to health by SFIs. Table 2 shows the estimated total burden of fungal
care providers in the public sector is 2.3 nurses per 5000 inhabi- infections, the number of infections classified according to the
tants and the ratio of midwives to health care providers in the main risk factors as well as the rate for 100,000 inhabitants.
Table 2
Estimated incidence and prevalence of most serious fungal diseases in Coˆte d’Ivoire.
Infection Number of infection per underlying disorder per year Total burden Rate/100K
None HIV/AIDS Respiratory Cancer ICU
Esophageal candidiasis – 4665 – – – 4665 19
Oral candidiasis – 17,280 – – – 17,280 69
Candida peritonitis – – – – 189 189 0.75
Candidaemia – – – 882 378 1260 5
Recurrent candida vaginitis (4Â/year) 421,936 – – – – 421,936 1675
ABPA – – 28,804 – – 28,804 114
SAFS – – 38,022 – – 38,022 151
CPA 6568 – – 6568 26
Invasive aspergillosis – 640 852 58 – 1550 6.15
Cryptococcal meningitis – 4590 – – – 4590 18.22
Pneumocystis pneumonia – 2640 – – – 2640 10.48
Histoplasmosis 513 – – 513 2.04
Tinea capitis 1,295,786 – – – – 1,295,786 5143
Fungal keratitis 3350 3350 13.3
Total burden estimated 1,721,072 30,328 74,246 940 567 1,827,204
ABPA: allergic bronchopulmonary aspergillosis; SAFS: severe asthma with fungal sensitisation; CPA: chronic pulmonary aspergillosis; ICU: intensive care unit.
3
D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx
Candida infections to be high. We calculated that SAFS affects 38,022 Ivorian adults
annually. ABPA and SAFS are collectively known as ‘‘fungal
There are no studies published on candidaemia or invasive asthma’’ which is responsive to antifungal therapy, and over
candidiasis in Coˆte d’Ivoire, so we have estimated a general rate of 40,000 adults probably suffer from this, as there is probably some
5/100,000 or 1260 cases of candidaemia annually [36]. Burned duplication between ABPA and SAFS prevalence. The long-term
patients are more likely to develop candidemia and other fungal natural history of fungal allergy is not well documented. Some
systemic lesions, as are HIV-positive patients [37]. Candidemia people have allergic fungal infection that comes and goes in
occurs in 2.5 to 7% of patients in intensive care units for burns severity, usually for unclear reasons. Mucus production and
[38]. In Coˆte d’Ivoire, the Abidjan center for burn victims receives mucosal swelling in the airways, nose and sinuses is the hallmark
about 500 burn patients a year. So nearly 25 will develop of fungal allergy.
candidemia [39]. We have assumed that 30% of candidaemia CPA is particularly common after pulmonary TB, and we
cases occur in intensive care. estimate and annual incidence of 1567 cases. However as this is a
For surgical ICU patients Candida peritonitis may develop in chronic condition, the overall prevalence will be higher, an
association with recurrent gastrointestinal perforations or anasto- estimated 6,568, of which 75% of cases are TB related and the
motic leakage after surgical intervention. Candida species are remainder to other pulmonary conditions such as sarcoidosis and
isolated between 70–90% of all patients with peritonitis [40]. Acute previous pneumothorax. Some patients have no underlying
peritonitis is a very common pathology. It occupies third place in condition at all, are usually misdiagnosed and TB. The key test
acute surgical abdomens after appendicitis and intestinal occlu- Aspergillus IgG antibody (or precipitins) is not available in Coˆte
sions. Its frequency is estimated, compared to all acute surgical d’Ivoire.
abdomens, to be 3% in France [41] and 20% in Mali [25]. If as in PCP exists in Coˆte d’Ivoire as evidenced by the autopsy study of
France we assume that the number of patients with intra- Coulibaly et al. who found in post-mortem a prevalence of 8.6% in
abdominal candidiasis is 50% of those with candidaemia [42], 70 HIV-infected patients [22]. This disease is caused by the
we estimate 189 such cases, but this may be a substantial opportunistic fungus P. jirovecii, which is a life-threatening
underestimate. infection in HIV/AIDS patients. Compared with adults, HIV-positive
Esophageal candidasis occur frequently in HIV-infected children had a high prevalence of P. jirovecii pneumonia and a low
patients. We estimate 4665 cases based on 20% of new HIV- prevalence of tuberculosis. Almost a third of HIV-positive children
infected patients and 0.5% of those on ARVs [43]. HIV/AIDS adds had PCP, according to Lucas et al. [10], a rate similar to that found in
nearly 2 million cases of oral thrush and > 500,000 cases of affected children in industralized countries but much higher than
oesophageal fungal infections annually in the world [44]. Oral the incidence in adults in Abidjan. We can estimate 2640 cases of
fungal infections are also common in babies, denture wearers, PCP, 990 in adults and 1650 in children. Several studies from
individuals using inhaled steroids for asthma, leukemia and different African countries found the incidence of PCP in HIV-
transplant patients and people receiving radiotherapy for head positive patients to vary from 1.25–49% [52].
and neck cancers, but we have been unable to estimate incidence of The relative infrequency of pneumocystosis is due to the low
these cases. prevalence of P. jirovecii in the African environment and lack of
rVVC is defined as four or more episodes of vulvovaginal appropriate diagnostic means, such as bronchoalveolar lavage and
candidiasis per year. This is a surprisingly common health problem trans-bronchial biopsy [53]. PCP may occur in other immunosup-
in sexually active women. rVVC is relatively common in Coˆte pression contexts, including solid organ transplant patients
d’Ivoire with C. albicans as the main causative agent. In Coˆte (kidney in particular), lymphoma or in patients receiving long-
d’Ivoire, a cross-sectional study of 400 women attending an STD term corticosteroids. In these cases the clinical picture is often
clinic found – 40% had evidence of VVC [45]. This same cohort was more brutal and the symptoms more frequently require admission
later re-analysed for rVVC and 23.5% of adult women were to intensive care unit. We were unable to assess the incidence of
apparently affected by rVVC [46]. This is however a select these cases in the absence of any data.
population and so the denomitor will be larger than 400, but it Invasive aspergillosis (IA) was estimated in leukaemia, lung
is not clear how large. Considering the actual adult female malignancies, COPD and HIV/AIDS. It was assumed that 10% of
population size, our estimate of rVVC prevalence is 421,936 cases acute myeloid leukaemia (and an equal number of other leukaemia
of rVVC at a rate of 1675 females per 100,000 person-years, but the and lymphoma patients), 2.6% of lung cancer patients [54] 1.3% of
real figure may be higher than this (and we have used 6% in our COPD hospital admissions (65,500) and 4% of HIV/AIDS deaths
estimate [Table 2]). About one in four women with VVC developed (16,000) [55] develop IA. We estimate an annual incidence of
rVVC, a significantly higher proportion than that reported in the 1550 cases. Very few of these diagnoses are currently established
literature, which ranges from 6 to 9% in European and North in Coˆte d’Ivoire and the optimal therapy of voriconazole is
American women [47,48]. This relatively high rate seems to unavailable. Globally over 300,000 individuals develop IA annually
corroborate previous studies suggesting an association of rVVCs with mortality rates ranging between 30% and 95% despite recent
with the black people [47,49,50], suggesting that genetic factors advanced HIV disease is a significant risk factor for the develop-
related to being black are responsible for the high susceptibility of ment of IA [56,57]. We known that the diagnosis of IA can be
women of this racial group to rVVC [50,51]. However, these challenging: host risk factors, clinical symptoms and radiological
putative genetic factors may not explain alone this relatively high findings must be put into context. Demonstration of morphological
rate of rVVC. Host-related and behavioural factors could also be features consistent with Aspergillus species or recovery of
associated with the occurrence of these recurrences. Aspergillus from a tissue sample is required to define a positive
(definitive) case. Obtaining tissue samples is often problematic in
Fungal related respiratory diseases these multi-morbid patients and the yield of fungi in culture is low,
difficult to interpret and prior antifungal prophylaxis further
Respiratory diseases including TB and asthma are major causes reduces its sensitivity [58,59]. Detection of Aspergillus antigen
of morbidity and hospital admissions in Coˆte d’Ivoire. Exacerba- (galactomannan) by Elisa or more recently immune-chro-
tions of asthma are common and may be driven by fungi, especially matographic technology (lateral flow devices) have been shown
Aspergillus spp, which is common in the environment and colonise to be much more sensitive than culture [60] but which
the airways. ABPA, CPA and SAFS frequencies are thus anticipated unfortunately are not yet available in the country. Just as IA cases
4
D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx
are challenging to diagnose, so is mucormycosis and we have not sub-Saharan Africa, where 70% of HIV/AIDS infections are concen-
estimated this life-threatening infection. trated. Neuromeningeal cryptococcosis (NMC) is the most serious
form of this infection. Death is inevitable in the absence of antifungal
Superficial fungal infections treatment and mortality remains high despite it. The incidence of this
pathology varies from 2 to 30% in HIV-positive patients. However,
Approximatively 25% of the general population have superficial epidemiological data of this pathology for Africa are limited. We
fungal infections of skin and nails, that are caused by dermato- estimated 4590 cases of NMC among adult HIV/AIDS patients, using a
phytes [61]. Children constitute the most affected population, 12.7% rate from a study Osazuwa et al. [19] However, two hospital-
especially in playgrounds, and thus are more likely to be in closer based studies in Coˆte d’Ivoire [68,69] reported a surprisingly low
contact with sources of fungal pathogens. Tinea capitis is very prevalence of rate of 0.6 and 3.6 and they cannot be generalized to the
common in children of sub-Saharan countries particularly in Coˆte population because of selection bias such that many patients with
d’Ivoire. In a large epidemiology study conducted in 2013, 13.9% of cryptococcal infection probably died before either being tested for
17,745 children were found to be positive, mainly with anthro- HIV or attending the clinic and by the lack of use of cryptococcal
pophilic dermatophytes, such as Trichophyton soudanense and antigenemia (CRAG) test which is not yet routinely available in
Microsporum langeroni [28]. We thus estimated that 1,295,786 hospitals. Cryptococcal antigenemia (CRAG) is detectable a median of
school children suffer from tinea capitis according to this 22 days before the onset of symptoms [70] and was shown to be 100%
epidemiological study. A similar pattern and frequency is seen sensitive for predicting the development of NMC in the first year of
in other West Africa countries including Nigeria [62], Guinea [63] ART [71], and is also associated with both NMC and mortality [72]. In
and Senegal [64]. view of these observations, screening for subclinical or asymptomatic
Superficial fungal infections are more rarely caused by non- infection by a serum CRAG assay in patients with advanced HIV
dermatophyte moulds (NDM) attacking the skin or nails. A infection, and giving antifungal therapy to those testing positive, may
longitudinal analysis of clinical data in the last 10 years shown prevent the development of NMC.
the increased prevalence of filamentous fungi involved in
superficial mycosis in Coˆte d’Ivoire. We have recently found Histoplasmosis
Aspergillus flavus (24.3%) Penicillium sp (22.9%), Fusarium sp (17.2%),
and Aspergillus niger (15.7%) from clinical samples primarily of Histoplasmosis is one of the opportunistic infections associated
nails but also intertrigo and mucosal infections (data unpublished). with AIDS. Most diagnoses of histoplasmosis are made post-
This data was confirmed by a recent review of 42 epidemiological mortem, as pre-mortem confirmatory tests are unavailable. The
studies from Bongomin et al. [65], showed that onychomycosis due autopsy study carried out in Coˆte d’Ivoire on 70 HIV-positive
to Aspergillus spp. varies between < 1 and 35% of all cases of patients who died revealed only 1.42% histoplasmosis [73]. Other-
onychomycosis in the general population and higher among wise, histoplasmosis in children or the immunocompetent subject
diabetic populations (accounting for up to 71%) and older people. are very rarely described and the clinical presentation is often
A single case of Conidiobolus infection of the face is described misleading. But in Coˆte d’Ivoire two cases of histoplasmosis in
[66]. A small number of mycetoma cases are described [67]. No immunocompetent patients are recorded: Histoplasma capsulatum
cases of sporotrichosis or chromoblastomycosis are described. var. capsulatum in a patient 36 years and without blemish [74] and
Fungal keratitis is seen clinically but rarely confirmed. Based on a Histoplasma capsulatum var.duboisii in a child [75]. We estimate
global analysis and using data from East Africa, we estimate 3,351 513 acute disseminated cases based on 1.42% of HIV-infected
cases annually. Clearly, this needs confirmation and it is likely that patients. Our estimate could be an underestimate with a 13% rate
all these eyes go blind, or have to be removed. of histoplasmosis among HIV-positive patients with persistent
fever and coughing associated with cutaneous lesions reported by
Cryptococcosis Mandengue et al. in Cameroon [76] and also the fact that we have a
few skilled personnel and facilities to make the diagnosis. In AIDS,
The emergence of Cryptococcus infections has dramatically 10–40% of patients present with skin lesions, which could facilitate
changed the epidemiology of cerebro-meningeal disease in rapid diagnosis if biopsied and examined histopathologically.
Table 3
Antifungal agents available in Coˆte d’Ivoire and whether included in the essential medecines list.
Antifungal agent Available On EML Hospital use Community pharmacy availability
Systemic agents
Amphotericin B Yes Yes Yes Yes
Lipid amphotericin B No – – –
Fluconazole Yes Yes Yes Yes
Itraconazole Yes Yes No Yes
Ketoconazole Yes Yes Yes Yes
Terbinafine Yes Yes Yes Yes
Griseofulvin Yes Yes Yes Yes
Flucytosine No – – –
Voriconazole No – – –
Capsofungin No – – –
Micafungin No – – –
Anidulafungin No – – –
Topical agents
Natamycin eye drops No – – –
Nystatin Yes – Yes Yes
Miconazole Yes Yes Yes Yes
Econazole Yes No Yes Yes
Cyclopiroxolamine No – – –
EML: WHO essential medicine list.
5
D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx
Antifungal therapy Patient consent for publication
Despite an increase in antifungal treatments over the past two Not required.
decades, treatment outcomes are still disappointing. Delays in
Funding
diagnosis and fungal identification greatly limit the efficacy of
therapy. Restrictions in route of administration, spectrum of This research did not receive any specific grant from funding agencies in
activity, and bioavailability of some antifungal, especially in HIV/ the public, commercial, or not-for-profit sectors.
AIDS and drug interactions hampers treatment success.
There are some antifungal agents available in Coˆte d’Ivoire
Contribution of authors
that are included in the country’s essential medicines list (Table
3), including fluconazole, itraconazole, amphotericin B
DWD, TOA and DK conceived and designed the protocol. DWD
[77]. Many are off patent with numerous generic formulations.
and DK drafted the manuscript with some adds of TOA. DWD, MD,
Very large numbers of topical azoles are available clinically for
IVB, FK, AM, REMN, KS and DK revised successive drafts of the
thrush and superficial infections; but these are not covered in
manuscript. All authors approved the final version of the
this report. Conventional amphotericin B treatment is largely
manuscript.
used in the hospitalized patient for systemic infection. In
Cameroon and Zimbabwe, about 100,000 days of amphotericin Disclosure of interest
B therapy are estimated annually. But in Mozambique and DRC,
The authors declare that they have no competing interest.
an estimated 200,000 days of amphotericin B therapy are needed.
Flucytosine is not available in Coˆte d’Ivoire although it has been
Acknowledgements
on the WHO EML since 2013. Itraconazole is not available in
Senegal, Gambia, Burundi and Eritrea, and probably some other
The authors thank all authors, clinicians and medical laboratory
countries. The total estimated market for itraconazole capsules
scientists who provided unpublished information from either
in Cote d’Ivoire and other antifungals has not been estimated.
previous works or clinical practice which was necessary in carrying
Natamycin eyedrops is also not available but critically important
out this work. We are also grateful to Ms. Hortance Aman and Mr.
for fungal keratitis.
Armand D. TRE BI respectively from Institut National de la
Because of the increasing of antifungal drug resistance,
Statistique (INS Coˆte d’Ivoire) and Department of Computing and
evidence emphasis on diagnostic testing has several merits. First,
Health Information (Ministry of Health and Hygiene, Coˆte d’Ivoire)
it can establish the correct diagnosis, with both immediate and
for their valuable contribution in National data searching and
longer term implications for therapy – cryptococcal meningitis
retrieval.
being an excellent example. Second, exclusion of a fungal diagnosis
can allow stopping of therapy – a good example is discontinuing
high dose (and often toxic) cotrimoxazole for PCP [78], as well as References
corticosteroids. Third, if a fungal diagnosis can be made, instead of
[1] Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC. Hidden
a bacterial diagnosis, such as CPA instead of smear negative
killers: human fungal infections. Sci Transl Med 2012;4:1–9 [165rv13].
tuberculosis, then antibacterial therapy can be stopped, contrib-
[2] RGPH; 2014 [Accessed 19th 2020. Available from: http://www.ins.ci/n/
uting to antimicrobial resistance (AMR) control [78]. Finally, documents/RGPH2014_expo_dg.pdf].
[3] UNAIDS; 2019 [Accessed 19th 2020. Available from: https://www.unaids.org/
increasing antifungal resistance, both acquired and intrinsic,
fr/regionscountries/countries/ctedivoire].
allows optimisation of antifungal therapy, instead of blind
[4] RASS; 2018 [Accessed 19th 2020. Available from: https://dipe.info/index.php/
empiricism before treatment performed. fr/component/jdownloads/download/ 6-rapport-annuel-sur-la-situation-sanitaire/
52-rapport-annuel-sur-la-situation-sanitaire-rass].
[5] Molloy SF, Chiller T, Greene GS, Burry J, Govender NP, Kanyama C, et al.
Conclusions Cryptococcal meningitis: a neglected NTD? PLoS Negl Trop Dis 2017;11:
e0005575.
[6] Ouattara B, Kra O, Adou-Bryn KD, Kouassi L, Toure K, Ouattara D, et al. Oral and
In conclusion, with almost 1.8 million cases among 25 million
esophageal mycosis in adult’s patients infected by HIV in university hospital of
people, severe fungal infections affect 7.25% of the population of
treichville (abidjan). Rev Col Odonto-Stomatol Afr Chir Maxillo-fac 2011;18:9–
Coˆte d’Ivoire. This result is comparable to that of Senegal, Ghana 12.
[7] Adoubryn KD, N’Gattia VK, Kouadio-Yapo GC, Nigue´ L, Zika DK, Ouhon J.
and Burkina Faso and other West African countries. Due to the
Epidemiology of otomycoses at the university hospital of Yopougon (Abid-
paucity of data, we believe that the true prevalence of fungal
jan-Ivory Coast). J Med Mycol 2014;24:e9–15.
infection may still be underestimated. As in other low and middle [8] Bosson-Vanga H, Konate´ A, Angora KE, Bonouman IA, Djohan V, Bedia AV, et al.
Profile of otomycosis diagnosed at Institut Pasteur of Cote D’Ivoire. Rev Int Sci
income countries, serious fungal infections remain neglected and
Med 2018;20:207–12.
underestimated in Coˆte d’Ivoire despite the rising trend globally
[9] Adou-Bryn KD, Ouhon J, Assoumou A, Kassi EA, Kone M, Therizol-Ferly M.
[79]. Most of these infections are undiagnosed or misdiagnosed Fungi and parasites isolated on the examination of 142 bronchial aspiration
liquids in Abidjan (Cote d’Ivoire). Med Afr Noir 1999;46:362–5.
leading to no treatment or incorrect treatment. Low indices of
[10] Lucas SB, Peacock CS, Hounnou A, Brattegaard K, Koffi K, Honde M, et al.
suspicion among clinicians and gaps in the availability of
Disease in children infected with HIV in Abidjan, Cote d’Ivoire. BMJ
diagnostics services and antifungal drugs are the identified causes. 1996;312:335–8.
[11] Koffi N, Ngom A, Kouassi B, Horo K, Gondola P, Aka-Danguy E. Profile of adult
Furthermore, the government and public health agencies have paid
asthmatic in hospital African environment (Abidjan). Med Afr Noir 2001;48:
less attention to fungal infections. Increasing awareness is a
477–80.
significant initial step to change the status quo. [12] Sakande J, Meite M, Seka J, Akre DP, Yapo-Cresoit A, Sombo MF. Allergic rhinitis
There is a need for the national government in Cote d’Ivoire to in Abidjan: epidemiological investigation and biological diagnosis. Med Afr
Noir 2008;55:114–8.
consider the implications of this increasing disease burden and
[13] GAFFI; 2020 [Accessed 19th 2020. Available from: https://www.gaffi.org/
facilitate better management of health in this neglected and media/academic-papers/].
usually vulnerable population. The negative effects of fungal [14] Ocansey BK, Pesewu GA, Codjoe FS, Osei-Djarbeng S, Feglo PK, Denning DW.
Estimated burden of serious fungal infections in Ghana. J Fungi (Basel)
infections on human health are not widely recognized despite the
2019;5:1–15.
fact that millions of people worldwide will contract life-threaten-
[15] Bamba S, Zida A, Sangare I, Cisse M, Denning DW, Hennequin C. Burden of
ing invasive infections. severe fungal infections in Burkina Faso. J Fungi (Basel) 2018;4:1–9.
6
D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx
[16] Chekiri-Talbi M, Denning DW. The burden of fungal infections in Algeria. J [45] Konate A, Yavo W, Kassi FK, Djohan V, Angora EK, Barro-Kiki PC, et al.
Mycol Med 2017;27:139–45. Aetiologies and contributing factors of vulvovaginal candidiasis in Abidjan
[17] To T, Stanojevic S, Moores G, Gershon AS, Bateman ED, Cruz AA, et al. Global (Cote d’Ivoire). J Mycol Med 2014;24:93–9.
asthma prevalence in adults: findings from the cross-sectional world health [46] Djohan V, Angora KE, Vanga-Bosson AH, Konate A, Kassi KF, Kiki-Barro PCM,
survey. BMC Public Health 2012;12:204. et al. Recurrent vulvo-vaginal candidiasis in Abidjan (Cote d’Ivoire): aetiology
[18] GLOBOCAN; 2018 [Accessed 19th 2020. Available from: https://gco.iarc.fr/ and associated factors. J Mycol Med 2019;29:127–31.
today/data/factsheets/populations/900-world-fact-sheets]. [47] Foxman B, Barlow R, D’Arcy H, Gillespie B, Sobel JD. Candida vaginitis:
[19] Osazuwa F, Dirisu JO, Okuonghae PE, Ugbebor O. Screening for cryptococcal self-reported incidence and associated costs. Sex Transm Dis 2000;27:
antigenemia in anti-retroviral naive AIDS patients in Benin city, Nigeria. Oman 230–5.
Med J 2012;27:228–31. [48] Foxman B, Muraglia R, Dietz JP, Sobel JD, Wagner J. Prevalence of recurrent
[20] Taylor SM, Meshnick SR, Worodria W, Andama A, Cattamanchi A, Davis JL, et al. vulvovaginal candidiasis in 5 European countries and the United States:
Low prevalence of Pneumocystis pneumonia (PCP) but high prevalence of results from an Internet panel survey. J Low Genit Tract Dis 2013;17:340–5.
pneumocystis dihydropteroate synthase (dhps) gene mutations in HIV-infec- [49] Geiger AM, Foxman B. Risk factors for vulvovaginal candidiasis: a case-control
ted persons in Uganda. PLoS One 2012;7:e49991. study among university students. Epidemiology 1996;7:182–7.
[21] Morrow BM, Hsaio NY, Zampoli M, Whitelaw A, Zar HJ. Pneumocystis pneu- [50] Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol 2016;214:
monia in South African children with and without human immunodeficiency 15–21.
virus infection in the era of highly active antiretroviral therapy. Pediatr Infect [51] Usluogullari B, Gumus I, Gunduz E, Kaygusuz I, Simavli S, Acar M, et al. The role
Dis J 2010;29:535–9. of human dectin-1 Y238X gene polymorphism in recurrent vulvovaginal
[22] Coulibaly G, N’Dhatz M, Domoua K, Aka-Danguy E, Traore F, Konan JB, et al. candidiasis infections. Mol Biol Rep 2014;41:6763–8.
Prevalence of pneumocystosis in HIV-infected subjects in a pneumo-phthi- [52] Alanio A, Denning DW. GAFFI fact sheet; 2017. [Accessed on 05 August 2020.
siology department: autopsy study carried out in Abidjan (Coˆte d’Ivoire). Rev Available from: https://www.gaffi.org/wp./PCP-GAFFI-December-2017.pdf]
Pneumol Clin 1994;50:116–20. [53] Birriel Jr JA, Adams JA, Saldana MA, Mavunda K, Goldfinger S, Vernon D, et al.
[23] Sawadogo D, Yapo AVDP, Sangare´ M, Tolo A, Yayo-Aye´ M. Caracte´ristiques Role of flexible bronchoscopy and bronchoalveolar lavage in the diagnosis of
e´pide´miologiques des patients atteints d’he´mopathies malignes a` Abidjan au pediatric acquired immunodeficiency syndrome-related pulmonary disease.
cours de la de´cennie 1995–2004. J Afr Cancer 2009;1:4–10. Pediatrics 1991;87:897–9.
[24] WHO. Country profile of environmental burden of disease: Cote d’Ivoire. [54] Yan X, Li M, Jiang M, Zou LQ, Luo F, Jiang Y. Clinical characteristics of 45 patients
Public Health and the Environment. Geneva, Switzerland: WHO; 2009. with invasive pulmonary aspergillosis: retrospective analysis of 1711 lung
[25] Konate´ MH. Abdomens aigus chirurgicaux dans le service de chirurgie ge´ne´- cancer cases. Cancer 2009;115:5018–25.
rale et pe´diatrique au CHU Gabriel Toure´; 2003 [Accessed on 15th August [55] Holding K, Dworkin MS, Wan PT, Hanson DL, Klevens RM, Jones JL, et al.
2020. Available from: wwwkeneyanet fmpos theses med pdf]. Aspergillosis among people infected with human immunodeficiency virus:
[26] Denning DW, Pleuvry A, Cole DC. Global burden of allergic bronchopulmonary incidence and survival. Clin Infect Dis 2000;31:1253–7.
aspergillosis with asthma and its complication chronic pulmonary aspergillo- [56] Kaur R, Mehra B, Dhakad MS, Goyal R, Dewan R. Pulmonary aspergillosis as
sis in adults. Med Mycol 2013;51:361–70. opportunistic mycoses in a cohort of human immunodeficiency virus infected
[27] Kwizera R, Musaazi J, Meya DB, Worodria W, Bwanga F, Kajumbula H, et al. patients: report from a tertiary care hospital in North India. Int J Health Sci
Burden of fungal asthma in Africa: a systematic review and meta-analysis. 2017;11:45–50.
PLoS One 2019;14:e0216568. [57] Denis B, Guiguet M, de Castro N, Mechai F, Revest M, Melica G, et al. Relevance
[28] Fulgence KK, Abibatou K, Vincent D, Henriette V, Etienne AK, Kiki-Barro PC, of EORTC criteria for the diagnosis of invasive aspergillosis in HIV-Infected
et al. Tinea capitis in schoolchildren in southern Ivory Coast. Int J Dermatol patients, and survival trends over a 20-year period in France. Clin Infect Dis
2013;52:456–60. 2015;61:1273–80.
[29] Brown L, Leck AK, Gichangi M, Burton MJ, Denning DW. The global incidence [58] De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al.
and diagnosis of fungal keratitis. Lancet Infect Dis 2020. http://dx.doi.org/ Revised definitions of invasive fungal disease from the European Organization
10.1016/S1473-3099(20)30448-5. for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative
[30] World Bank Reports. Cote d’Ivoire : contribution a` l’analyse de la pauvrete´. Group and the National Institute of Allergy and Infectious Diseases Mycoses
th
[Published June 29 2006; Accessed on 11th November 2020. Available from: Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813–
documentsworldbankorg curated] 21.
[31] RASS; 2016 [Accessed on 5th August 2019. Available from: https://dipe.info/ [59] Horvath JA, Dummer S. The use of respiratory-tract cultures in the diagnosis of
index.php/fr/component/jdownloads/download/ invasive pulmonary aspergillosis. Am J Med 1996;100:171–8.
6-rapport-annuel-sur-la-situation-sanitaire/ [60] Moura S, Cerqueira L, Almeida A. Invasive pulmonary aspergillosis: current
52-rapport-annuel-sur-la-situation-sanitaire-rass]. diagnostic methodologies and a new molecular approach. Eur J Clin Microbiol
[32] Echimane AK, Ahnoux AA, Adoubi I, Hien S, M’Bra K, D’Horpock A, et al. Cancer Infect Dis 2018;37:1393–403.
incidence in Abidjan, Ivory Coast: first results from the cancer registry, 1995– [61] Havlickova B, Czaika VA, Friedrich M. Epidemiological trends in skin mycoses
1997. Cancer 2000;89:653–63. worldwide. Mycoses 2008;51:2–15.
[33] Stucky Hunter E, Richardson MD, Denning DW. Evaluation of LDBio Aspergillus [62] Grace M, Ayanbimpe HT, Diya A, Wapwera S. Tinea capitis among primary
ICT lateral flow assay for IgG and IgM antibody detection in chronic pulmonary schoolchildren in some parts of central Nigeria. Mycoses 2008;51:336–40.
aspergillosis. J Clin Microbiol 2019;57:1–12. [63] Cisse M, Diare FS, Kaba A, Magassouba E, Mambu K, Ecra EJ. Tinea capitis in
[34] Bigby TD, Margolskee D, Curtis JL, Michael PF, Sheppard D, Hadley WK, et al. department of dermatology and venerology in the university hospital of
The usefulness of induced sputum in the diagnosis of Pneumocystis carinii Donka at Conakry, Guinea. Bull Soc Pathol Exot 2006;99:32–3.
pneumonia in patients with the acquired immunodeficiency syndrome. Am [64] Ndiaye D, Se`ne PD, Faye JLNB, Ndir O. Tinea of the scalp diagnosed in Senegal. J
Rev Respir Dis 1986;133:515–8. Med Mycol 2009;19:262–9.
[35] Nowaseb V, Gaeb E, Fraczek MG, Richardson MD, Denning DW. Frequency of [65] Bongomin F, Batac CR, Richardson MD, Denning DW. A review of onychomy-
Pneumocystis jirovecii in sputum from HIV and TB patients in Namibia. J Infect cosis due to Aspergillus species. Mycopathologia 2018;183:485–93.
Dev Ctries 2014;8:349–57. [66] Taylor GD, Sekhon AS, Tyrrell DL, Goldsand G. Rhinofacial zygomycosis caused
[36] Arendrup MC. Epidemiology of invasive candidiasis. Curr Opin Crit Care by Conidiobolus coronatus: a case report including in vitro sensitivity to
2010;16:445–52. antimycotic agents. Am J Trop Med Hyg 1987;36:398–401.
[37] Bruck HM, Nash G, Stein JM, Lindberg RB. Studies on the occurrence and [67] Adoubryn KD, Koffi KE, Troh E, Doukoure B, Kouadio-Yapo CG, Ouhon J, et al.
significance of yeasts and fungi in the burn wound. Ann Surg 1972;176:108– Native mycetoma of Coˆte d’Ivoire: epidemiological and etiological features of
10. confirmed cases. J Med Mycol 2009;19:71–6.
[38] Zorgani A, Franka RA, Zaidi MM, Alshweref UM, Elgmati M. Trends in nosoco- [68] Kadjo K, Ouattara B, Adoubryn KD, Kra O. Current aspects of neuromeningeal
mial bloodstream infections in a burn intensive care unit: an eight-year cryptococcosis in adult subjects infected with HIV in the internal medicine
survey. Ann Burns Fire Disasters 2010;23:88–94. department of the university hospital of Treichville d’Abidjan (Ivory Coast). J
[39] Le Floch R, Naux E, Arnould JF. Infections fongiques des bruˆle´s : revue. Ann Mycologie Med 2011;21:6–9.
Burns Fire Disasters 2015;28:94–104. [69] Bedia-Tanoh AV, Kassi KF, Barro-Kiki PM, Angora KE, Bosson-Vanga AHAK,
[40] Raaijmakers R, Schroder C, Monnens L, Cornelissen E, Warris A. Fungal et al. Cryptoccocal meningitis in Abidjan. Rev Int Sci Med 2018;20:301–5.
peritonitis in children on peritoneal dialysis. Pediatr Nephrol 2007;22:288– [70] French N, Gray K, Watera C, Nakiyingi J, Lugada E, Moore M, et al. Cryptococcal
93. infection in a cohort of HIV-1-infected Ugandan adults. AIDS 2002;16:1031–8.
[41] Lorand I, Molinier N, Soles J, Douchez F, Gayral F. Results of laparoscopic [71] Jarvis JN, Lawn SD, Vogt M, Bangani N, Wood R, Harrison TS. Screening for
treatment of perforated ulcers. J Chir 1999;124:149–53. cryptococcal antigenemia in patients accessing an antiretroviral treatment
[42] Montravers P, Dupont H, Eggimann P. Intra-abdominal candidiasis: the gui- program in South Africa. Clin Infect Dis 2009;48:856–62.
delines-forgotten non-candidemic invasive candidiasis. Intensive Care Med [72] Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, Kambugu A, et al.
2013;39:2226–30. Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths
[43] Smith E, Orholm M. Trends and patterns of opportunistic diseases in Danish among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL
AIDS patients 1980–1990. Scand J Infect Dis 1990;22:665–72. who start HIV therapy in resource-limited settings. Clin Infect Dis
th
[44] How common are fungal diseases? [Published June 18 2011, updated July 2010;51:448–55.
2019; Accessed on 12 November 2020. Available from: http:// [73] Ndhatz M, Domoua K, Coulibaly G. Pulmonary pathology and retroviral
wwwfungalinfectiontrustorg/wp-content/uploads/2019/08/ infection. Necropsy study of 70 cases in Abidjan. Rev Pneum Clin How-Common-are-Fungal-Diseases-v122pdf] 1993;49:211–21.
7
D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx
[74] Kouassi YI, Ahogo KC, Koui BB, Ecra EJ, Kouassi KA, Kaloga M, et al. Histoplas- [77] GAFFI; 2016. [Accessed on 05th August 2020. Available from: https://www.
mosis to Histoplasma capsulatum var capsulatum: a lethal form in an immu- gaffi.org/antifungal-drug-maps]
nocompetent patient. Rev Int Sci Med 2016;18:123–6. [78] Denning DW, Perlin DS, Muldoon EG, Colombo AL, Chakrabarti A, Richardson
[75] Ahogo K, Sangare´ A, Kaloga IGM, Kassi K, et al. e. Cutaneous histoplasmosis due MD, et al. Delivering on antimicrobial resistance agenda not possible
to Histoplasma capsulatum variety duboisii in an immune competent child. without improving fungal diagnostic capabilities. Emerg Infect Dis
About one case in Abidjan, Coˆte d’Ivoire. Bull Soc Pathol Exot 2009;102:147–9. 2017;23:177–83.
[76] Mandengue CE, Ngandjio A, Atangana PJ. Histoplasmosis in HIV-infected [79] Pierre Aubry, Gau¨ ze`re B-A. Mycoses profondes. Actualite´s 2018; 2018 [Dis-
persons, Yaounde, Cameroon. Emerg Infect Dis 2015;21:2094–6. ponible sur : wwwmedecinetropicalecom].
8